Role of NUB1 in inclusion body formation in synucleinopathies

NUB1 在突触核蛋白病包涵体形成中的作用

• 批准号: 20300123
• 负责人: WAKABAYASHI Koichi
• 金额: $ 11.56万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20300123/
• 关键词: 神経変性疾患; パーキンソン病; レビー小体型認知症; 脳神経疾患; 神経科学; 病理学

In human Lewy body disease (LBD), PK-resistant α-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant α-synuclein was detected in the presynaptic fraction in Tg mice and human LBD. We further demonstrated that, in the brains of patients with LBD, NUB1 accumulates in the presynapses in the hippocampus, cerebral neocortex, and substantia nigra in which PK-resistant α-synuclein is deposited. Endogenous NUB1 also accumulated with PK-resistant α-synuclein in the presynapses of Tg mice that express human α-synuclein with an A53T mutation. Immunoelectron microscopy showed that NUB1 was localized to presynaptic nerve terminals where no abnormal filaments were seen. Biochemical analyses showed that NUB1 coexists with abnormal α-synuclein in the brains of LBD patients. These findings suggest that NUB1 along with abnormal α-synuclein is involved in the pathogenesis of LBD.

在人类路易体病中，耐PK的α-突触核蛋白沉积在路易体和路易氏神经突起，以及不同脑区的突触前，包括海马体、颞叶皮质和黑质。生化分析表明，在TG小鼠和人类LBD的突触前部分检测到对PK具有抗性的α突触核蛋白。我们进一步证明，在腰椎病患者的大脑中，NUB1积聚在海马区、大脑新皮质和黑质的突触前，其中沉积了对PK具有抗性的α-突触核蛋白。在表达带有A53T突变的人α-突触蛋白的转基因小鼠的突触前，内源性NUB1也与PK抗性α-突触蛋白积聚在一起。免疫电子显微镜显示，NUB1定位于突触前神经末梢，未见异常细丝。生化分析显示，在腰椎间盘突出症患者脑组织中，NUB1与异常的α-突触核蛋白共存。提示NUB1与α-突触核蛋白异常共同参与了腰椎退行性变的发病机制。

项目成果

Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinonathies of the brain

周围神经系统参与突触核蛋白病、tau蛋白病和其他大脑神经退行性蛋白病

• 发表时间: 2010
• 期刊: Acta Neuropathologica
• 影响因子: 12.7
• 作者: Wakabayashi K.;et al
• 通讯作者: et al

Chorea-acanthocytosis with upper motor neuron degeneration and 3419_3420 delCA and 3970_3973 delAGTC VPS13A mutations

舞蹈病-棘红细胞增多症伴上运动神经元变性和 3419_3420 delCA 和 3970_3973 delAGTC VPS13A 突变

• 发表时间: 2010
• 期刊: Acta Neuropathologica 119
• 作者: Miki Y.;et al.
• 通讯作者: et al.

Existence of proteinase K-resistant α-synuclein is human Lewy body disease and A53T α-synuclein transgenic mice.

存在蛋白酶K抗性α-突触核蛋白的是人路易体病和A53T α-突触核蛋白转基因小鼠。

• 发表时间: 2010
• 作者: Tanji K;Mori F;Kakita A;Takahashi H;Wakabayashi K
• 通讯作者: Wakabayashi K

Alteration of biochemical and pathological properties of TDP-43 protein by a lipid mediator, 15-deoxy-Δ12,14-prostaglandin J2

脂质介质 15-脱氧-Δ12,14-前列腺素 J2 改变 TDP-43 蛋白的生化和病理特性

• DOI: 10.1016/j.expneurol.2010.01.007
• 发表时间: 2010
• 期刊: Experimental Neurology
• 影响因子: 5.3
• 作者: Hai;K. Tanji;H. Yoshida;M. Hayakari;T. Shibata;F. Mori;K. Uchida;K. Wakabayashi
• 通讯作者: K. Wakabayashi

Serine 129 phosphorylation of a-synuclein induces unfolded protein response-mediated cell death

α-突触核蛋白丝氨酸 129 磷酸化诱导未折叠蛋白反应介导的细胞死亡

• 发表时间: 2008
• 期刊: Journal of Biological Chemistry 283
• 作者: Sugeno N;et.al.
• 通讯作者: et.al.